Conventional cancer therapy is plagued by the problem that the generally attainable targeting ratio (ratio of administered dose localizing to tumor versus administered dose circulating in blood or ratio of administered dose localizing to tumor versus administered dose migrating to bone marrow) is low. Improvement in targeting ratio dose to tumor is sought.
One method employed in efforts to improve targeting ratio is to decrease the serum concentration of a compound. One method of decreasing the serum concentration of an administered compound is to subsequently administer a molecule designed to be eliminated rapidly via the liver and to bind to the first administered compound. Galactose-HSA-biotin conjugates, discussed in PCT patent application No. PCT/US93/05406 facilitate elimination of circulating targeting agent-streptavidin conjugates from the bloodstream. Galactosylated antibodies directed to a portion of a previously administered molecule have also been employed for this purpose.
In addition, the liver is susceptible to a variety of conditions for which liver delivery of an active agent would be useful. In these circumstances, delivery of active agent via the hepatic artery has been proposed. This methodology is invasive and, therefore, other methods of active agent delivery to the liver are sought.